Testosterone (T) was given to normal men with and without the concomitant administration of the aromatase inhibitor, α¹-testolactone (Teslac), to examine the role of peripheral aromatization of T in gonadotropin regulation. When T was administered alone by continuous iv infusion (15 mg/day for 4 days), serum T increased 3-fold (P <0.01) and estradiol (E) increased by 50% (P < 0.01). These changes were associated with a 50% decrease in serum LH and FSH concentrations (P < 0.01). When T was infused into men taking Teslac (2000 mg/day), serum T levels doubled (P < 0.01), but E levels did not change (13.4 ± 1.5 vs. 13.5 ± 1.0 pg/ml; P = NS). This pattern of plasma steroids, increased T and unchanged E, was also associated with significantly decreased serum LH and FSH concentrations (14.5 ± 0.4 vs. 8.0 + 0.4 mlU/ml and 9.9 ± 2.5 vs. 5.8 ± 0.1 mlU/ml, respectively; P < 0.01). These data support the hypothesis that T or one of its metabolites can modulate LH and FSH secretion independently of peripheral aromatization to E.